The compound of d-2-aminobutanol is currently prepared by resolution of its racemic mixture with L(+)-tartaric acid. Approximately fifty percent (50%) of the material is washed in the l-stream together with the resolving agent because it is unavailable for recycle. A method aimed at direct synthesis of the desired d-isomer would constitute a great advance in the art.
Synthesis of optically active amino acids (II) by asymmetric hydrogenation of their dehydro precursors is well known in the art; W. S. Knowles, M. J. Sabacky and B. D. Vineyard, Chem. Commun., 1445 (1963), 10 (1972); W. S. Knowles, M. J. Sabacky and B. D. Vineyard, Ann. N.Y. Acad. Sci., 172, 232 (1970); Chem. Engineering News, Feb. 7, 1972, p. 4; Chem. Week, Feb. 9, 1972, p. 41; T. P. Dang and H. B. Kagan, Chem. Commun. 481, (1971); H. B. Kagan and T. P. Dang, J. Am. Chem. Soc., 91, 6429 (1972). ##STR1##
Asymmetric hydrogenation of .alpha.-acylaminocrotonic acid ##STR2## followed by reduction of the carboxyl group to hydroxymethyl could in principle result in d-2-aminobutanol, but the reduction conditions for the second step are rather severe. Alternate routes involving asymmetric hydrogenation of .alpha.-acylamino crotyl alcohol and its O-acyl derivatives (IV) were investigated.
______________________________________ ##STR3## a, R.sub.3 =acetyl b, R.sub.3 =benzoyl c, R.sub.3 =hydrogen ______________________________________
The O-acetate (IVa) and the O-benzoate (IVb) however, suffered hydrogenolysis of the ester groups and the products formed were acylamino alkanes rather than the alcohol esters. Hydrogenolysis can be prevented by hydrogenating the free alcohol (IVc) prepared from either (IVa) or (IVb) by treatment with ammonia or amines. ##STR4## Enamido alcohols such as VII are difficult to prepare. Reported reactions involves lithium borohydride or calcium borohydride reduction of azlactones such as (VI): ##STR5## This reaction works well only with azlactones where R.sub.1 is phenyl or another bulky substituent, and is characterized by generally poor yields.
The synthesis of the instant invention, as set forth below, has certain novel elements. ##STR6## The second route is based on asymmetric reduction of 4-ethyl-oxazolinones. Asymmetric or nonasymmetric hydrogenation of 4-ethyl oxazolinones (VII) to 4-ethyl oxazolidones (VIII) which can be hydrolyzed respectively to d-2-aminobutanol or dl-2-aminobutanol has not been reported in the literature. The synthetic route is novel while the catalysts are conventional or newly discovered by other workers. The novel synthetic routes of the instant invention provide flexibility for the production of d-2-aminobutanol as well as dl-2-aminobutanol in that they may both be prepared from the same substrate using chiral or achiral catalysts.
The most closely related art of which Applicant is aware is the Abstract of German Offen. No. 2,408,171, which discloses certain compounds of the formula: ##STR7##